Relations between brain tissue loss, CSF biomarkers, and the ApoE genetic profile: A longitudinal MRI study

Previously it was reported that Alzheimer's disease (AD) patients have reduced beta amyloid (Aβ_1-42) and elevated total tau (t-tau) and phosphorylated tau (p-tau_181p) in the cerebrospinal fluid (CSF), suggesting that these same measures could be used to detect early AD pathology in healthy elderly individuals and those with mild cognitive impairment (MCI). In this study, we tested the hypothesis that there would be an association among rates of regional brain atrophy, the CSF biomarkers Aβ_1-42, t-tau, and p-tau_181p and apolipoprotein E (ApoE) ε4 status, and that the pattern of this association would be diagnosis-specific. Our findings primarily showed that lower CSF Aβ_1-42 and higher tau concentrations were associated with increased rates of regional brain tissue loss and the patterns varied across the clinical groups. Taken together, these findings demonstrate that CSF biomarker concentrations are associated with the characteristic patterns of structural brain changes in healthy elderly and mild cognitive impairment subjects that resemble to a large extent the pathology seen in AD. Therefore, the finding of faster progression of brain atrophy in the presence of lower Aβ_1-42 levels and higher tau levels supports the hypothesis that CSF Aβ_1-42 and tau are measures of early AD pathology. Moreover, the relationship among CSF biomarkers, ApoE ε4 status, and brain atrophy rates are regionally varying, supporting the view that the genetic predisposition of the brain to beta amyloid and tau mediated pathology is regional and disease stage specific.